Synthesis of C6-amino agarose and evaluation of its antibacterial activity.

In this paper, the biologically inert agarose was selectively modified at C6 of ß-d-Galp units to produce an amino derivative with antibacterial property. The synthetic route involved the preparation of tosyl and azido agarose intermediates. All the polysaccharide derivatives were characterized by mono- and bidimensional 1H and 13C NMR and FT-IR analysis. A water-soluble amino polymer (Mw = 39,000 g mol-1, DSamino = 0.50) was produced by partial acid hydrolysis showing bactericidal and bacteriostatic activity against P. aeruginosa (ATCC 9027), S. aureus (ATCC 6538), and E. coli (ATCC 25922), with MIC values lower than 2.5 mg mL-1 and MBC values ranging from 2.5 to 5.0 mg mL-1.

Semi-synthesis of N-alkyl-kappa-carrageenan derivatives and evaluation of their antibacterial activity.

In this article, we describe the semi-synthesis of N-alkyl-kappa-carrageenan derivatives and their antibacterial activity against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8739), and Pseudomonas aeruginosa (ATCC 9027). Kappa-carrageenan was submitted to partial acid hydrolysis promoting the selective cleavage of α-glycosidic bonds involving 3,6-anhydro-α-D-Galp units, giving rise to reducing low-molecular weight polysaccharide fragments, which were reacted with alkylamines of varying chain lengths by reductive amination. The carrageenan derivatives were characterized by HPSEC-MALLS-RID and 1D and 2D 1H and 13C NMR spectroscopy. The antibacterial activity of N-alkyl-kappa-carrageenan derivatives was compared with N-alkyl-(1-deoxylactitol-1-yl)-amines using a microdilution test, which indicated that inhibitory activity was dependent on the degree of substitution by hydrophobic groups at the polysaccharide structure. Comparing the effect of different N-alkyl chains, those with longer chains showed higher activity.

Development and Evaluation of Orodispersible Tablets Containing Ketoprofen.

BACKGROUND: Orodispersible Tablets (ODTs) are an option to facilitate the intake of pharmaceutical solid dosage forms, which dissolve in the mouth within 30 seconds releasing the drug immediately with no need for water intake or chewing. OBJECTIVE: The main goal of our study is the technological development of lactose-free orodispersible tablets that contain ketoprofen. METHODS: We assessed different variables during the pharmaceutical development of ODTs: compression techniques conducted after a wet granulation process, aiming to optimize the flow properties of the formulation, and a suspension freeze-drying molded in blisters. We developed three formulations for each method, each containing one of the superdisintegrants: croscarmellose, crospovidone, or starch glycolate. RESULTS: During the production of ODTs, we performed quality control of the granulation process, since the production of pellets contributed to the enhancement of the disintegration time and content homogeneity. Quality control tests for ODTs produced by freeze-drying were also satisfactory, despite significant changes in the final physical aspect of these products when compared to that of ODTs produced by compression. In addition, the disintegration times of ODTs produced by freeze-drying were substantially higher. Furthermore, these tablets displayed greater friability and pose a challenge to the control of a standard individual weight. CONCLUSION: Among the superdisintegrants, croscarmellose contributed most significantly to reduce the disintegration time and to dissolve KTP effectively in 20 minutes.

Solid-State Characterization and Compatibility Studies of Penciclovir, Lysine Hydrochloride, and Pharmaceutical Excipients.

The physical and chemical characterization of the solid-state properties of drugs and excipients is fundamental for planning new formulations and developing new strategies for the treatment of diseases. Techniques such as differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy are among the most commonly used techniques for these purposes. Penciclovir and lysine are individually used to treat the herpes virus. As such, the development of a formulation containing both drugs may have therapeutic potential. Solid-state characterization showed that both penciclovir and lysine were crystalline materials with melting points at 278.27 °C and 260.91 °C, respectively. Compatibility studies of penciclovir and lysine indicated a possible interaction between these substances, as evidenced by a single melting point at 253.10 °C. The compatibility of several excipients, including ethylenediaminetetraacetic acid, cetostearyl alcohol, sodium lauryl sulphate, di-tert-butyl methyl phenol, liquid petrolatum, methylparaben, nonionic wax, paraffin, propylene glycol, and propylparaben, was evaluated in ternary (penciclovir-lysine-excipient) mixtures (1:1:1, w/w/w) to determine the optimal formulation. The developed formulation was stable under accelerated and ambient conditions, which demonstrated that the interaction between penciclovir and lysine was suitable for the development of a formulation containing both drugs.

Solid-State Characterization of Different Crystalline Forms of Sitagliptin.

Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-4, used for the treatment of type 2 diabetes mellitus. The crystal structure of active pharmaceutical solids determines their physical and chemical properties. The polymorphism, solvates and hydrates can influence the free energy, thermodynamic parameters, solubility, solid-state stability, processability and dissolution rate, besides directly affecting the bioavailability. Thus, the physicochemical characterization of an active pharmaceutical ingredient is required to guarantee the rational development of new dosage forms. In this context, we describe herein the solid-state characterization of three crystalline forms of sitagliptin: sitagliptin phosphate monohydrate, sitagliptin phosphate anhydrous and sitagliptin base form. The investigation was carried out using differential scanning calorimetry (DSC), thermogravimetry (TG)/derivative thermogravimetry (DTG), spectroscopic techniques, X-ray powder diffraction (XRPD) and morphological analysis by scanning electron microscopy. The thermal analysis revealed that during the dehydration of sitagliptin phosphate monohydrate (Tpeak = 134.43 °C, ΔH = -1.15 J g-1) there is a characteristic crystalline transition event, which alters the physicochemical parameters of the drug, such as the melting point and solubility. The crystalline behavior of sitagliptin base form differs from that of sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous, mainly with regard to the lower temperature of the fusion event. The melting point (Tpeak) values obtained were 120.29 °C for sitagliptin base form, 206.37 °C for sitagliptin phosphate monohydrate and 214.92 °C for sitagliptin phosphate anhydrous. In relation to the thermal stability, sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous showed a slight difference; however, both are more thermostable than the base molecule. Therefore, through this study it was possible to establish the most suitable crystalline form of sitagliptin for the development of a safe, effective and appropriate pharmaceutical dosage form.

Colorimetric microdilution assay: Validation of a standard method for determination of MIC, IC50%, and IC90% of antimicrobial compounds.

The emergence of multiresistant bacteria directly impacts on the search for new compounds with antimicrobial activity, and it is important the improvement of new techniques are able to determine the minimum inhibitory concentration (MIC) of antimicrobial compounds. The microdilution technique is widely used for saving culture media, reagents and compounds to be tested. However, the literature does not describe a colorimetric method capable of correlating absorbance with concentration of viable microorganisms (CFU mL-1). Therefore, the novelty of this work was the standardization and validation of a colorimetric and quantitative method capable of determining the MIC of several compounds with antimicrobial activity and the conversion of absorbance values to CFU mL-1. The conditions carried out for the method were: the use of 0.125% (w/v) 2,3,5-triphenyltetrazolium chloride (TTC) solution added after 22 h of incubation at 35 °C, followed by 2 more hours of incubation and subsequent reading in a spectrophotometer. The tested microorganisms were: Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027) and Candida albicans (ATCC 10231). The method was validated and showed linearity (R2 > 0.95), precision (RSD <26%), accuracy (75% to 122%) and robustness (p > 0.05). The validated parameters ensured the harmonization of methodology to determine not only MIC as well as inhibitory concentrations of 50% (IC50%) and 90% (IC90%) of the antimicrobial compounds.

Chemical, Antioxidant, and Antimicrobial Evaluation of Essential Oils and an Anatomical Study of the Aerial Parts from Baccharis Species (Asteraceae).

The aim of this study was to evaluate the chemical, antioxidant, and antimicrobial activity of the essential oils as well as the anatomy of the aerial parts from Baccharis aracatubaensis, Baccharis burchellii, and Baccharis organensis owing to the therapeutic potential of Baccharis. The volatile constituents were analyzed using GC/MS, the antioxidant activity was evaluated by oxygen radical absorbance capacity (ORACFL ) and DPPH assays, and the antimicrobial activity by a microdilution technique. Of the 56 compounds identified, only seven (ß-caryophyllene, γ-muurolene, bicyclogermacrene, ß-germacrene, spathulenol, τ-muurolol, and α-cadinol) were common in the three specimens studied. Of these, γ-muurolene was found abundantly in B. aracatubaensis, while bicyclogermacrene was abundant in B. burchellii and B. organensis. The essential oils exhibited antioxidant activity in the ORACFL (>500.0 µmol TE g-1 ) and DPPH assays. However, they did not exhibit any antimicrobial activity. Secretory ducts and flagelliform glandular trichomes were observed in the anatomical study of all the Baccharis species studied.

Thermal and chemical characterization of Dicksonia sellowiana extract by means of thermal analysis

Abstract Dicksonia sellowiana Hook., Dicksoniaceae, is a tree-fern which is being recently used in medicine mainly for its phytotherapic activities. While several other studies have focused on D. sellowiana extract characterization in terms of its biological and antioxidant activity, the novelty of this work aims to understand the fate of this extract during thermal disposal through thermogravimetry/differential thermal analysis, thermogravimetry/mass spectrometry, Fourier transform infrared spectroscopy and elemental analysis, to further characterize this plant's extract. Thermal analysis revealed mass loss within three well-defined steps, with the respective mass signals represented generated during heating. Light-volatiles were released during the first step, with release of NO2, CO2, and ethanol in the following, as a result of extract pyrolytic decomposition. Furthermore, mass signals variation during heating indicated the release of harmless by products in contrast to other pharmaceutical and personal care products. Finally, chemical characterization confirmed the observed under thermal analysis suggesting a highly polar structure within extract's composition.

Development and validation of a stability-indicating LC method for the determination of venlafaxine in extended-release capsules and dissolution kinetic studies.

A stability-indicating reversed-phase high-performance liquid chromatography method is developed and validated for the determination of venlafaxine hydrochloride (VEN) in extended-release capsules containing spherical beads and for dissolution studies. The method is carried out on a Luna C(18) column (250 mm x 4.6 mm) maintained at 35 degrees C. The mobile phase is composed of ammonium-acetate buffer 32 mM, adjusted to pH 6.8 with phosphoric acid-acetonitrile-methanol (62:30:8, v/v/v), run at a flow rate of 1.0 mL/min, and detection at 226 nm. Validation parameters such as the specificity, linearity, precision, accuracy, and robustness are evaluated, giving results within the acceptable range. In order to evaluate the best dissolution condition, the dissolution profiles are performed under different conditions, such as media (HCl, water, phosphate buffer), apparatus (I and II), and dissolution rates (50, 75, and 100 rpm). The kinetics release mechanism is evaluated by fitting different models, such as the zero order rate, first order, and Higuchi. Moreover, the proposed method is successfully applied for the assay of VEN in extended-release capsules.

Physico-chemical solid-state characterization of omeprazole sodium: thermal, spectroscopic and crystallinity studies.

The physical characterization of active pharmaceutical substances is crucial to the successful development of the final drug product. The different solid forms and variations in the degree of crystallinity can lead to significantly different physical and chemical properties, including color, morphology, stability, dissolution and bioavailability. In the case of omeprazole sodium (OMS), its chemical structures contain a specific number of water molecules (hydrate). The behavior of pharmaceutical hydrates has become the object of increasing attention over the past decade, primarily due to the potential impact of hydrates on the development process and dosage form performance. The present study was designed to characterize and evaluate the crystallinity of omeprazole sodium, dehydrated omeprazole sodium (DOMS) and omeprazole free base (OM) using a variety of techniques including thermal analysis (thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC)), diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, scanning electron microscopy (SEM) and X-ray powder diffraction (XRPD). Furthermore, an NMR spectroscopy study was also carried out to clarify the conformation and crystal structure.

Development and validation of an RP-HPLC method to quantitate acyclovir in cross-linked chitosan microspheres produced by spray drying.

An accurate, simple, reproducible, and sensitive liquid chromatographic method is developed and validated to quantitate acyclovir (ACV) in cross-linked chitosan microspheres produced by spray drying. The analysis is carried out using a reversed-phase C18 column with UV-vis detection at 254 nm. The mobile phase is diluted with pure water and acetonitrile (95:5 v/v) at a flow-rate of 0.8 mL/min. The parameters used in the validation process are: linearity, range, quantitation limit, detection limit, accuracy, specificity precision, and ruggedness. The retention time of acyclovir is approximately 3.5 min with symmetrical peaks. The linearity in the range of 1-10 microg/mL presents a correlation coefficient of 0.9999. The chitosan and the tripolyphosphate in the formulation do not interfere with the analysis, and the recovery is quantitative. Results are satisfactory, and the method proves to be suitable to quantitate ACV in cross-linked chitosan microspheres.

Development and validation of an HPLC method to quantify camptothecin in polymeric nanocapsule suspensions.

A simple, rapid, and sensitive reversed-phase column high-performance liquid chromatographic method was developed and validated to quantify camptothecin (CPT) in polymeric nanocapsule suspensions. The chromatographic separation was performed on a Supelcosil LC-18 column (15 cm x 4.6 mm id, 5 microm) using a mobile phase consisting of methanol-10 mM KH2PO4 (60 + 40, v/v; pH 2.8) at a flow rate of 1.0 mL/min and ultraviolet detection at 254 nm. The calibration graph was linear from 0.5 to 3.0 microg/mL with a correlation coefficient of 0.9979, and the limit of quantitation was 0.35 microg/mL. The assay recovery ranged from 97.3 to 105.0%. The intraday and interday relative standard deviation values were < 5.0%. The validation results confirmed that the developed method is specific, linear, accurate, and precise for its intended use. The current method was successfully applied to the evaluation of CPT entrapment efficiency and drug content in polymeric nanocapsule suspensions during the early stage of formulation development.